A meibomian gland is lipid-producing gland enclosed in both the upper and lower eyelids (palpebra), and secretes a lipid through an opening situated on a conjunctiva side from eyelashes of eyelids. A lipid layer constituting a tear fluid contains a lipid supplied from the meibomian glands as a component, and prevents the tear fluid from evaporating from an eye surface. It is known that patients with meibomian gland dysfunction or meibomitis develop hyperevaporative dry eye, keratoconjunctiva epithelial disorder, corneal epithelial erosion and corneal ulcer, which are associated with dry eye, and the like, since the meibomian gland shows functional deterioration and secretes a lipid at a lower level.
In addition, the cornea consists of epithelium and an external limiting membrane (Bowman's membrane), stroma, a internal limiting membrane (Descemet's membrane) and endothelium. Since the cornea is located at the frontmost part of the eyeball, it is susceptible to external environmental influence, as a result of which various disorders are developed. Examples of the diseases associated with wound or defect of corneal epithelial cells include dry eye syndrome, corneal ulcer, superficial punctuate keratitis, corneal epithelial erosion, ocular allergic diseases associated with corneal lesion such as vernal conjunctivitis, atopic keratoconjunctivitis etc., and the like.
On the other hand, PPAR is one kind of intranuclear receptors expressed in most vertebrates, and is considered to be a transcription factor group closely related to the intracellular sugar or lipid metabolism and cell differentiation. As the subtype, α, δ and γ-types are known. PPARδ is sometimes indicated as PPARβ (non-patent document 1).
As for the distribution of PPAR in the ocular tissue, expression of PPARα and β in the corneal epithelial cells of rabbit is known (non-patent document 2).
There have been reported that 5-[4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy)benzyl]thiazolidine-2,4-dione considered to mainly have a PPARγ activation action can be utilized as a therapeutic agent for keratoconjunctival disorders (patent documents 1 and 2), and PPARα, δ or γ agonist is administered for the treatment of ocular diseases (conjunctivitis, dry eye syndrome, keratitis etc.) (patent document 3). In addition, it is known that PPARα is distributed in the liver, kidney and the like, and acts on lipid metabolism and transportation. Furthermore, it has also been reported that an agonist thereof can be utilized as a therapeutic agent for corneal diseases (patent document 4). PPARδ agonists have been reported to promote proliferation and differentiation of rat sebaceous gland epithelial cells (non-patent document 3) and promote wound healing of the skin (non-patent document 4). Besides the above, a method of stimulating proliferation of β-cell by administering a non-thiazolidinedione PPAR ligand and a GLP-1 derivative (patent document 5), inhibition of proliferation of leukemia cell, prostate cancer cell and the like by pioglitazone (PPARγ agonist) (patent document 6) and the like are known.
However, many aspects of the expression and function of PPARα, δ or γ in each animal species and each tissue or cell are yet to be clarified, and whether a PPARδ agonist is useful for ocular diseases in human is not correctly known.    patent document 1: WO2005/039574    patent document 2: JP-A-2001-39976    patent document 3: WO2002/076177    patent document 4: JP-A-2005-008570    patent document 5: WO2002/69994    patent document 6: WO1998/25598    non-patent document 1: J Med Chem 2000, 43: 527-550    non-patent document 2: J Biol Chem 2000, 275: 2837    non-patent document 3: Molecular Genetic and Metabolism 2001, 74: 362-369    non-patent document 4: Am J Clin Dermatol 2003, 4(8): 523-530